New insights into endometriosis
Research directed by a University of Liverpool scientist has raised hopes that novel drugs which inhibit telomerase – currently being trialled as potential cancer therapies – could also offer a more effective treatment for endometriosis.
Endometriosis is the most common benign gynaecological disease – afflicting up to twenty women in every hundred, which equates to around 89m women around the world. Many sufferers experience severe recurring pain, but others may experience symptoms more akin to irritable bowel syndrome. They may also find it impossible to conceive: endometriosis is one of the leading causes of female infertility.
|
The artist Adelaide Damoah marking the beginning of Endometriosis Awareness Week by leading a communal scream – drawing attention to the fact that endometriosis takes an average 8 years to diagnose; 65% of women are misdiagnosed initially; and nearly 50% see five or more practitioners before they obtain the correct diagnosis. |
The only reliable diagnosis involves invasive laparoscopy. It’s not known what causes endometriosis, and there is currently no cure – though surgery may provide respite for a while. There are also hormone-based treatments, but they are not entirely effective and can cause undesirable side-effects.
New hypothesis
Most women with the condition have inappropriate tissue deposits in the pelvic cavity – in the ovaries, fallopian tubes, uterine ligaments and/or the intestines, but very rarely these tissue deposits can also be found in other parts of the body, even in the lungs. The disease gets its name from the endometrium – the tissue lining the uterus – because these tissue deposits closely resemble it.
Implanted patch of endometrial tissue overlying the bladder.
The most widely accepted theory of the origin of the disease is that endometrial tissue from the uterine cavity is expelled in to the pelvic cavity as a result of retrograde menstruation, giving rise to endometriotic deposits. However, most women exhibit retrograde menstruation – yet only 15-20 per cent get endometriosis.
Both the endometrial cells lining the normal uterine cavity in these women and the cells in the abnormal deposits are able to survive and proliferate, which made Dr Dharani Hapangama wonder whether endometriosis might be associated with abnormal expression of telomerase and telomere lengthening in the endometrium.
Telomeres are like caps on the end of chromosomes, protecting them from damage and degradation. They get shorter each time the cells divide and eventually somatic cells lose the ability to proliferate and die because of the associated DNA dysfunction. Telomerase is an enzyme that mends telomeres; high levels of it have been linked to cancer – and the defining feature of cancer cells is their ability to keep proliferating indefinitely.
Two years ago, Dr Hapangama set out to test her hypothesis in a pilot study funded by the University of Liverpool.
Research design & findings
Fifty six women took part in the study – 29 with symptomatic, surgically diagnosed endometriosis and 27 who were fertile and shown through laparoscopy to be symptom-free. Endometrial biopsies were taken from both groups at two time points: three weeks into their menstrual cycle (around the time of conception), and shortly before the end of their cycle.
Dr Hapangama analysed samples from each biopsy, using immunohistochemistry techniques to evaluate levels of telomerase and an oestrogen receptor. Samples were also sent to Newcastle University, where the length of the telomeres was measured using quantitative PCR – the first time this analysis has been done on benign endometrial tissue.
Analysis of the two teams’ results revealed that mean telomere lengths were significantly longer in the endometria of women suffering from endometriosis, particularly during the embryo implantation window of the cycle – and there was good correspondence between mean telomere lengths and levels of telomerase immunoreactivity.
These results suggest that aberrant endometrial expression of telomerase mediates alterations in cell fate that enhance proliferation, contributing to the pathogenesis of endometriosis. “In other words”, says Dr Hapangama, “endometriosis may happen because sufferers shed endometrial tissue in the course of their monthly periods, and these cells are different to those in women who don’t develop the disease.
“In normal women these cells die because they can’t continue dividing; as a consequence they become prone to DNA damage and programmed cell death. In the endometriosis sufferers these cells may have the ability to remain alive and even continue proliferating after they have been shed – giving rise to endometriotic deposits elsewhere in the body. If so, they may have this ability as a result of expressing telomerase.”
The study’s findings were published in Human Reproduction in May 2008, and were featured shortly afterwards by Faculty 1000 Medicine, which highlights the most interesting papers published in medicine based on the recommendations of ~2,500 leading clinicians and researchers around the world.
12%
8%
7%
18%
52%
11%
36%
1%
